LAUSR

Aneuploidy, or an abnormal chromosome copy number, is a characteristic feature of cancer, which plays an important role in cancer initiation and progression [1]. Aneuploidy prevalence patterns are tissue-specific, with different chromosomes gained or lost across cancer types [1–3]. Whole-genome duplication (WGD), also known as whole-genome doubling, occurs in nearly a third of human tumors, usually at the early stages of tumorigenesis [4, 5]. It is known that tumors that have undergone WGD are more permissive to aneuploidy, but whether WGD also affects aneuploidy patterns has remained an open question (Figure 1). To address this intriguing question, we recently analyzed 5,586 clinical tumor samples that had not undergone WGD (WGD-) and 3,435 tumors that had (WGD+) from The Cancer Genome Atlas (TCGA), across 22 tumor types [6]. WGDand WGD+ tumors showed distinct aneuploidy patterns; WGD+ tumors were more chromosomally unstable and were more permissive to aneuploidy, presenting not only more aneuploidies in general but also a wider variety of events. Chromosome loss was more common in WGD+ than in WGDtumors, suggesting that genome doubling might “buffer” the detrimental effect of losing DNA content. In addition,